Transesophageal Echocardiography - Dysphagia Risk in Acute Stroke (TEDRAS): a prospective, blind, randomized and controlled clinical trial.

BACKGROUND AND PURPOSE: Dysphagia is common in acute stroke and leads to worse overall outcome. Transesophageal echocardiography (TEE) is used in the diagnostic evaluation of stroke with regard to its etiology and is a known cause of postoperative dysphagia in cardiac surgery. The prevalence of dysphagia in acute stroke patients undergoing TEE remains unknown. The aim of the Transesophageal Echocardiography - Dysphagia Risk in Acute Stroke (TEDRAS) study was to assess the influence of TEE on swallowing among patients who have experienced acute stroke. METHODS: The TEDRAS study was a prospective, blind, randomized, controlled trial that included two groups of patients with acute stroke. Simple unrestricted randomization was performed, and examiners were blinded to each other's results. Swallowing was tested using flexible endoscopic evaluation of swallowing (FEES) at three different time points in the intervention group (24 h before, immediately after and 24 h after TEE) and in the control group (FEES on three consecutive days and TEE earliest after the third FEES). Validated scales were used to assess dysphagia severity for all time points as primary outcome measures. RESULTS: A total of 34 patients were randomized: 19 to the intervention group and 15 to the control group. The key findings of the repeated-measures between-group comparisons were significant increases in the intervention group for the following dysphagia measures: (1) secretion severity score (immediately after TEE: P < 0.001; 24 h after TEE: P < 0.001) and (2) Penetration-Aspiration Scale score for saliva (immediately after TEE: P < 0.001; 24 h after TEE: P = 0.007), for small (immediately after TEE: P = 0.009) and large liquid boli (immediately after TEE: P = 0.009; 24 h after TEE: P = 0.025). CONCLUSION: The results indicate a negative influence of TEE on swallowing in acute stroke patients for at least 24 hours.

Patients with manifest hepatic encephalopathy can reveal impaired thermal perception.

OBJECTIVES: Previous evoked potential studies indicated central impairments of somatosensory function in patients suffering from hepatic encephalopathy (HE). The aim of this study was to quantify the somatosensory perception in patients with minimal and overt HE. MATERIALS AND METHODS: Forty-two patients with liver cirrhosis and HE up to grade 2 and 12 age-matched healthy controls underwent a comprehensive graduation of HE including the West Haven criteria, the critical flicker frequency (CFF), and neuropsychometric testing. Quantitative sensory testing, standardized by the German Research Network on Neuropathic Pain, was performed on both hands. RESULTS: Pain and mechanical detection thresholds were unchanged in HE. Tests of thermal processing revealed that patients with HE of grade 2 perceive cold at lower temperatures (cold detection threshold) and need a higher temperature difference to distinguish between warm and cold (thermal sensory limen). These impairments correlated with the CFF. A correction for attention deficits by performing partial correlations using neuropsychometric test results canceled these correlations. CONCLUSIONS: The present findings demonstrate an impairment of temperature perception in HE. The extent of this impairment correlates with HE severity as quantified by the CFF. The attenuation of the correlations after correction for attention deficits suggests a strong role of attention deficits for the impaired thermal perception. Thus, it provides initial evidence for a central impairment of thermal processing in HE due to alterations in high-level processes rather than due to peripheral neuropathic processes, which are a frequent complication in patients with liver cirrhosis.

Cortical activation associated with asterixis in manifest hepatic encephalopathy.

OBJECTIVES: Severe hepatic encephalopathy gives rise to asterixis, a striking motor symptom also called flapping tremor, which is characterized by a sudden ceasing of muscle tone in all muscles of a limb. In this study, we aimed at scrutinizing the cortical activation associated with asterixis and unraveling the underlying pathophysiological mechanisms. MATERIAL AND METHODS: We recorded simultaneously neural activity with magnetoencephalography (MEG) and muscle activity with surface EMG in nine patients with manifest hepatic encephalopathy showing asterixis. Asterixis events were detected semiautomatically and served as triggers for averaging MEG signals. Evoked responses averaged time-locked to asterixis events were subjected to equivalent current dipole (ECD) modeling. Additionally, we localized the strongest cortico-muscular coherence in the frequency of the co-occurring tremulousness. RESULTS: Evoked fields averaged time-locked to asterixis events were best explained by a single dipolar source in the contralateral primary motor cortex (M1, Talairach coordinates of mean localization: -40, -20, and 64; Brodmann area 4). This dipole showed a twofold field reversal, that is biphasic wave, with frontal dipole orientation at 49 ms before flap onset and 99 ms after flap onset. Conversely, two maxima with occipital dipole orientation were observed 2 ms and 160 ms after flap onset. Cortico-muscular coherence for the tremulousness was likewise localized in the contralateral M1 confirming earlier findings in the present patient cohort. CONCLUSIONS: Our results reveal an involvement of M1 in the generation of asterixis. As also tremulousness, also called mini-asterixis, was shown to originate in M1, asterixis and mini-asterixis may share common pathophysiological mechanisms.

Differential modulation of STN-cortical and cortico-muscular coherence by movement and levodopa in Parkinson's disease.

Previous research suggests that oscillatory coupling between cortex, basal ganglia and muscles plays an important role in motor behavior. Furthermore, there is evidence that oscillatory coupling is altered in patients with movement disorders such as Parkinson's disease (PD). In this study, we performed simultaneous magnetoencephalography (MEG), local field potential (LFP) and electromyogram (EMG) recordings in PD patients selected for therapeutic subthalamic nucleus (STN) stimulation. Patients were recorded (i) after withdrawal of anti-parkinsonian medication (OFF) and (ii) after levodopa administration (ON). We analyzed STN-cortical and cortico-muscular coherence during static forearm contraction and repetitive hand movement in order to evaluate modulations of coherence by movement and medication. Based on previous results from studies investigating resting state coherence in PD patients, we selected primary motor cortex (M1) and superior temporal gyrus (STG) as regions of interest. We found beta coherence between M1 and STN to be suppressed by administration of levodopa. M1-muscular coherence was strongly reduced in the alpha and beta band during repetitive movement compared to static contraction, but was unaffected by administration of levodopa. Strong STG-STN but not STG-muscular coherence could be observed in the alpha band. Coherence with STG was modulated neither by movement nor by medication. Finally, we found both M1-STN and M1-muscular beta coherence to be negatively correlated with UPDRS akinesia and rigidity sub-scores in the OFF state. The present study provides new insights into the functional roles of STN-cortical and cortico-muscular coherence and their relationship to PD symptoms. The results indicate that STN-cortical and cortico-muscular coupling are correlated, but can be modulated independently. Moreover, they show differences in their frequency-specific topography. We conclude that they represent partly independent sub-loops within the motor system. Given their negative correlation with akinesia, neither can be considered "antikinetic".

Distinct oscillatory STN-cortical loops revealed by simultaneous MEG and local field potential recordings in patients with Parkinson's disease.

Neuronal oscillations are assumed to play a pivotal role in the pathophysiology of Parkinson's disease (PD). Neurons in the subthalamic nucleus (STN) generate oscillations which are coupled to rhythmic population activity both in other basal ganglia nuclei and cortical areas. In order to localize these cortical areas, we recorded local field potentials (LFPs) and magnetoencephalography (MEG) simultaneously in PD patients undergoing surgery for deep brain stimulation (DBS). Patients were withdrawn from antiparkinsonian medication and recorded at rest. We scanned the entire brain for oscillations coherent with LFPs recorded from the STN with a frequency domain beamformer. Coherent activity in the low (12-20 Hz) and high (20-35 Hz) beta range was found in the ipsilateral sensorimotor and the premotor cortex. Coherence in the alpha range (7-12 Hz) was observed at various locations in the ipsilateral temporal lobe. In a subset of subjects, the superior temporal gyrus consistently showed coherent alpha oscillations. Our findings provide new insights into patterns of frequency-specific functional connectivity between basal ganglia and cortex and suggest that simultaneous inter-regional interactions may be segregated in the frequency domain. Furthermore, they demonstrate that simultaneous MEG-LFP recordings are a powerful tool to study interactions between brain areas in PD patients undergoing surgery for DBS.

Motor impairment in liver cirrhosis without and with minimal hepatic encephalopathy.

AIM: Manifest hepatic encephalopathy (HE) goes along with motor symptoms such as ataxia, mini-asterixis, and asterixis. The relevance of motor impairments in cirrhotics without and with minimal HE (mHE) is still a matter of debate. PATIENTS AND METHODS: We tested three different groups of patients with liver cirrhosis: no signs of HE (HE 0), mHE, and manifest HE grade 1 according to the West Haven criteria (HE 1). All patients (n = 24) and 11 healthy control subjects were neuropsychometrically tested including critical flicker frequency (CFF), a reliable measure for HE. Motor abilities were assessed using Fahn Tremor Scale and International Ataxia Rating Scale. Fastest alternating index finger movements were analyzed for frequency and amplitude. RESULTS: Statistical analyses showed an effect of HE grade on tremor and ataxia (P < 0.01). Additionally, both ratings yielded strong negative correlation with CFF (P < 0.01, R = -0.5). Analysis of finger movements revealed an effect of HE grade on movement frequency (P < 0.03). Moreover, decreasing movement frequency and increasing movement amplitude parallel decreasing CFF (P < 0.01, R = 0.6). CONCLUSION: Our results indicate that ataxia, tremor, and slowing of finger movements are early markers for cerebral dysfunction in HE patients even prior to neuropsychometric alterations becoming detectable.

Impaired cerebral oscillatory processing in hepatic encephalopathy.

OBJECTIVE: Hepatic encephalopathy (HE) is characterized by neuropsychological and motor deficits. The present study tested the hypothesis that worsening of motor and sensory symptoms of HE results from a common basic deficit in the cerebral oscillatory processing within the human motor and visual system. METHODS: We investigated in 32 patients with liver cirrhosis and HE grades 0-2 critical flicker frequency (CFF) and cortico-muscular (M1-EMG) coherence as a measure of coupling between the surface EMGs of hand muscles and primary motor cortex (M1) activity recorded non-invasively with magnetoencephalography (MEG) during forearm elevation. RESULTS: Patients with HE-grade 2 developed excessive M1-EMG coherence at low frequencies. In contrast, maximum M1-EMG coherence in patients with no HE showed frequency and amplitude in the physiological range. CFF was continuously reduced with worsening grades of HE. Correlation analysis revealed significant correlation between the frequency of M1-EMG coherence and CFF. CONCLUSIONS: Taken together, we demonstrate that increased grades of HE lead to a pathological M1-EMG drive which is reduced in frequency. These effects are correlated with an impaired perception of oscillatory visual stimuli. SIGNIFICANCE: The results suggest that pathological oscillatory neural processing in different human cerebral systems may represent a basic mechanism for the clinical manifestation of HE.

Trends in suspected and recognized occupational respiratory diseases in Germany between 1970 and 2005.

BACKGROUND: Respiratory diseases represent a major proportion of occupational diseases in many countries. Little information is available about their incidences over the past several decades. METHODS: Based on the reports of the three German federal accident insurance agencies, the numbers of suspected and recognized cases of occupational respiratory diseases between 1970 and 2005 were collected and combined. The trends in the rates per 100,000 insured workers were calculated. RESULTS: In total, a decline in occupational respiratory diseases since 1998 could be observed. This trend is mainly based on the decrease in non-malignant respiratory diseases due to silica and obstructive airway diseases. In contrast, asbestos-induced diseases showed a leveling off or an increase (mesothelioma) during the last 10years. CONCLUSIONS: Although trends in occupational disease may be influenced by several factors, the presented data indicate that prevention has been effective in reducing some ofthe most frequent occupational respiratory diseases in Germany.

Distinct cortical responses evoked by electrical stimulation of the thalamic ventral intermediate nucleus and of the subthalamic nucleus.

OBJECTIVE: To investigate the spatial and temporal pattern of cortical responses evoked by deep brain stimulation (DBS) of the subthalamic nucleus (STN) and ventral intermediate nucleus of the thalamus (VIM). METHODS: We investigated 7 patients suffering from Essential tremor (ET) and 7 patients with Parkinson's Disease (PD) following the implantation of DBS electrodes (VIM for ET patients, STN for PD patients). Magnetoencephalography (MEG) was used to record cortical responses evoked by electric stimuli that were applied via the DBS electrode in trains of 5 Hz. Dipole fitting was applied to reconstruct the origin of evoked responses. RESULTS: Both VIM and STN DBS led to short latency cortical responses at about 1 ms. The pattern of medium and long latency cortical responses following VIM DBS consisted of peaks at 13, 40, 77, and 116 ms. The associated equivalent dipoles were localized within the central sulcus, 3 patients showed an additional response in the cerebellum at 56 ms. STN DBS evoked cortical responses peaking at 4 ms, 11 ms, and 27 ms, respectively. While most dipoles were localized in the pre- or postcentral gyrus, the distribution was less homogenous compared to VIM stimulation and partially included prefrontal brain areas. CONCLUSION: MEG enables localization of cortical responses evoked by DBS of the VIM and the STN, especially in the sensorimotor cortex. Short latency responses of 1 ms suggest cortical modulation which bypasses synaptic transmission, i.e. antidromic activation of corticofugal fiber pathways.

Autofeedback suppression of growth hormone (GH) secretion in transgenic mice expressing a human GH reporter targeted by tyrosine hydroxylase 5'-flanking sequences to the hypothalamus.

Transgenic mice expressing a tyrosine hydroxylase-human (h) GH fusion gene in the hypothalamus exhibit a dwarf phenotype. The GH feedback mechanism(s) underlying the growth retardation in these animals was investigated by assessing peptide and messenger RNA (mRNA) levels of the hormones of the hypothalamic-GH-IGF-I axis. Pituitary GH content, hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) content, and serum IGF-I levels were measured by RIA. mRNA levels of hypothalamic GHRH and SRIH and of pituitary GH and the GHRH receptor were measured by Northern blot hybridization. Transgenic mice of both sexes and their wild-type littermates were studied at 2-4 months of age. The pituitary GH content was markedly reduced by 85% in male and by 87% in female transgenic mice compared to that in wild-type controls (P < 0.01 for both). The pituitary GH mRNA content was also decreased by 73% (P = 0.002) in transgenic male mice. Circulating IGF-I levels were significantly reduced by 66% and 68% in male and female transgenic mice, respectively (P = 0.001). The hypothalamic GHRH content was significantly reduced by 19% and 33% (P < 0.05) in male and female transgenic mice, respectively. No significant difference was detected, however, in the hypothalamic SRIH content between wild-type and transgenic mice. Hypothalamic GHRH mRNA levels were significantly decreased by 35% (P = 0.002) in transgenic male mice compared to those in wild-type littermates. In contrast, SRIH mRNA was not significantly changed. An even greater reduction (61%; P = 0.003) was observed in pituitary GHRH receptor mRNA in transgenic mice. These data indicate that the GH deficiency and dwarf phenotype of the tyrosine hydroxylase-hGH transgenic mouse can be attributed primarily to impaired hypothalamic GHRH production. The mechanism of GH feedback inhibition appears to involve direct suppression of GHRH gene expression by locally produced hGH in the hypothalamus.

Density of sympathetic axons in sural nerve biopsies of neuropathy patients is related to painfulness.

In this study, differences of unmyelinated nerve fiber density in sural nerve biopsy material from patients suffering from neuropathies of unknown origin with (n=14) or without pain (n=13) were analyzed. Immunocytochemistry was applied to differentiate afferent sensory and efferent sympathetic nerve fibers. All patients were evaluated for deficits of small fiber function with thermotesting, quantitative sudomotor-axon reflex-testing and testing of painfulness of mechanical stimuli before performing the biopsy. No difference was found between patients with and without pain concerning clinical deficits or results in any of the neurophysiological examinations. There were also no histopathological differences concerning the density of afferent C-fibers. However, absolute and relative density of efferent sympathetic nerve fibers was significantly higher in patients with painful neuropathy (P<0.001), although none of the patients demonstrated clinical sympathetic abnormalities. We conclude that an imbalance between afferent and sympathetic nerve fiber density in the periphery may contribute to neuropathic pain even in those patients without obvious clinical autonomic disturbances.

Expression of a fusion gene consisting of the mouse growth hormone-releasing hormone gene promoter linked to the SV40 T-antigen gene in transgenic mice.

Limited information is available concerning the regulation of growth hormone-releasing hormone (GHRH) gene expression in the hypothalamus, largely because of the lack of a suitable cellular model. In an attempt to immortalize hypothalamic GHRH-producing neurons, we have generated a transgenic mouse model which expresses the simian virus 40 (SV40) T-antigen gene (Tag) under the control of the GHRH gene promoter. The transgene contains approximately 5 kb of mouse GHRH gene sequences, including 3.5 kb of the 5'-flanking region, the entire hypothalamic exon 1 and 1.5 kb of intron 1, fused to the SV40 Tag gene. This construct was microinjected into fertilized oocytes. Fourteen of 96 mice born had integrated the transgene. These mice were fertile and showed no signs of central or peripheral tumors. The pattern of expression of the SV40 Tag gene was analyzed in four different transgenic lines by RT-PCR. The tissues tested include: hypothalamus, pituitary, cortex, cerebellum, spinal cord, adrenal, testis, spleen and lung. Transgene expression was consistently detected in the hypothalamus of all lines. In addition, SV40 Tag expression was also detected in the hypothalamus by Northern blot analysis in two of the transgenic lines. SV40 Tag expression was also detected in the testis of all transgenic lines by RT-PCR. This result was not expected since the GHRH gene sequences present in the transgene do not include the testis-specific transcription initiation site previously described. This suggests that GHRH gene expression in the mouse testis can be directed by regulatory sequences located downstream of the testis specific transcription start site. We conclude that the promoter region of the GHRH gene included in this construct contains the regulatory elements necessary to drive hypothalamic and testis expression in vivo. In addition, all mice from one of the transgenic lines developed cataracts in both eyes. SV40 Tag expression was detected not only in eyes with cataracts, but also, to a lesser extent, in eyes from other transgenic lines. Furthermore, the endogenous GHRH gene was found to be expressed in the eyes of normal mice.

Neuropeptide content of peripheral nerve in relation to nerve function in neuropathy.

OBJECTIVE: In this study an APAAP (alcalic-phophatase-anti-alcalic-phosphatase) technique was used to distinguish afferent (calcitonin-gene-related-peptide (CGRP) or substance-P-(SP) positive) and autonomic (tyrosin-hydroxylase (TH), neuropeptide Y (NPY) or vasoactive-intestinal-polypeptide- (VIP) positive) nerve fibers in sural nerve biopsy material from patients with moderate sensory neuropathy. A panneuronal marker against protein-gene-product 9.5 (PGP 9.5) was used for detection of the total amount of nerve fibers. Second aim was to analyze possible correlations between the impairment in tests for the function of unmyelinated fibers (i.e. thermal threshold testings, sensitivity to painful mechanical stimulation, axon reflex-mediated flare reaction and sudomotor activity) and nerve pathology. RESULTS: A high correlation between CGRP and SP (p < 0.00003) and between TH and NPY, respectively, (p < 0.004) was found, but not between afferent and autonomic markers or between specific markers and PGP 9.5. While no correlations between sensory neuropeptides (CGRP and SP) and specific testings of afferent fiber function or between neuropeptide content and clinical data could be demonstrated, there was a significant correlation between the TH content of the sural nerve and the sweat output, stimulated by acetylcholine iontophoresis at the level of the foot (p = 0.019) and upper leg (p = 0.011). CONCLUSION: This study demonstrates the possibility of visualizing subgroups of unmyelinated nerve fibers in sural nerve biopsies selectively with this technique. The density of TH-positive sympathetic nerve fibers, but not the density of afferent c-fibers, is correlated with corresponding results in specific tests of c-fiber function.

The vampire as a metaphor for working with childhood abuse.

The characteristics of the vampire legend are compared to those associated with childhood abuse in terms of the role of the abuser and the abused and of the interchange between them. Principles of analytical psychology are used as a template through which the drama of vampire/abuser and victims can be understood, with the vampire representing the negative aspect of the healer archetype.

Metabolic disorders in patients with calcium urolithiasis.

In the last two decades, intensive research work has been done in the field of urolithiasis. Due to improved and extended diagnostic methods, it has been recognized that metabolic disturbances play an important role in stone disease.

[Oxalate stone prophylaxis by alkalinizing therapy (author's transl)]. / Oxalatsteinprophylaxe durch Alkali-Therapie.

Hypocitraturia was found in 75% of oxalate stone formers, and combined with hypercalciuria in 27%. By short-term alkalinizing therapy (3 weeks) with sodium-potassium-citrate (Uralyt-U) a 118% increase in citrate- and a 29.5% decrease in calcium excretion could be achieved in 71 patients. There was no change in the 24 h urinary excretion of oxalate, urate, magnesium and phosphate. In 10 recurrent oxalate stone formers long-term (10 to 20 months) alkalinizing therapy was performed. The quantitative effect on the excretion of citrate and calcium remained unchanged. Seven patients, who have completed at least one year of therapy have had no recurrence of stones.

[2,8-dihydroxyadenine urinary calculus: the significance of exact physical calculus analysis]. / 2,8-Dihydroxyadeninharnstein: Die Bedeutung der exakten physikalischen Steinanalyse.

A 21-year-old female patient was treated with Uralyt-U for 3 months for a radiolucent kidney stone. During this therapy the stone increased significantly in volume. After treatment by ESWL, the stone was analyzed by a chemical method and by X-ray diffraction. Calcium phosphate and urate were detected by the chemical method and 2,8-dihydroxyadenine by X-ray diffraction. This case report emphasizes the importance of precise stone analysis for medical treatment is emphasized.

[Diagnosis and therapy of non-germ cell testicular tumors. Organ preservation or orchiectomy?]. / Diagnostik und Therapie nichtgerminaler Hodentumoren. Organerhalt oder Orchiektomie?

Between 1980 and 1990, 670 testicular examinations were performed. Testicular palpation and ultrasonography were carried out. A total of 588 patients (87.8%) had malignant testicular tumors; 82 patients (12.2%) were found to have nongerminal testicular and paratesticular tumors. Intraoperative frozen section histology and tumor size determined the subsequent procedure. In cases of epidermal cysts, adenomatoid tumors and fibrous pseudotumors, the testicle was preserved in the majority of cases. Leydig's cell tumor, Sertoli's cell tumor and dermoid cysts were removed together with the testicle because it was not clear if they were benign. During the postoperative follow-up period, there was no evidence of local recurrence or metastases in any of the patients.

Practical applications from chaos theory to the psychotherapeutic process, a basic consideration of dynamics.

This essay contains speculations about the import of some ideas from chaos theory for psychotherapeutic process. Brief consideration is given to areas of psychology in which such ideas have been applied, as well as some ideas on psychic energy. Then, using a psychodynamic perspective as a base, three aspects of psychotherapy are addressed, the container, the process, and the clinician as the agent of change. A central idea is that the emotional experience of chaos is a necessary developmental step. It is important for the therapist to recognize whether a client is avoiding this experience or is overwhelmed by this experience.

Chaos, an omen of transcendence in the psychotherapeutic process.

Here some of the basic ideas assembled under the recently coined term chaos theory are applied to the process of psychotherapy. Utilizing some ideas from chaos theory, "chaos" is defined in psychological terms as a state of overwhelming anxiety and is interpreted as the first indication of potential psychological growth. The concepts of Analytical Psychology and the modality of sandtray therapy are used to illustrate the type of therapeutic approach this theoretical work proposes in the transcendent cycle. Psychotherapy simply facilitates a transformation, wherein clients are guided through the chaos they are experiencing so that they may grow beyond their current psychological limitations.